Intracerebroventricular Administration Of Corticotropin-releasing Factor Research Articles

Corticotropin-releasing factor disrupts sensory responses of brain noradrenergic neurons.

In order to elucidate the possible role of noradrenergic neurons of the nucleus locus coeruleus (LC) in stress responses, the effects of corticotropin-releasing factor (CRF) on LC neuronal activity were characterized. In haloth-aneanesthetized rats, intracerebroventricular administration of CRF was found to have two distinct actions: A dose-dependent increase in spontaneous discharge activity was observed 3 min after peptide injection, with 1.0 and 3.0 micrograms CRF increasing activity by 7 +/- 2 and 47 +/- 12%, respectively; Ala14CRF (3.0 micrograms), an inactive analogue of CRF, had no effect on LC spontaneous discharge rates. These results confirm and extend previous studies of CRF activation of LC basal discharge activity; additionally, CRF (1.0 and 3.0 micrograms) disrupted sensory responses of LC cells to sciatic nerve stimulation. As previously reported, responses of LC neurons to electrical stimulation of the sciatic nerve usually consisted of a brief activation beginning 20-40 ms after stimulus followed by a period of relatively suppressed activity lasting 100-200 ms. CRF attenuated both components. Responses plotted as normalized, cumulative histograms became more linear in the presence of CRF (1.0 and 3.0 micrograms), suggesting that discharge rates during phasic responses to sciatic stimulation were similar to spontaneous rates. Statistical comparison using the Kolmogorov-Smirnoff test or correlation coefficients demonstrated that both 1.0 and 3.0 micrograms CRF reduced response components, while 0.3 micrograms and Ala14CRF (3.0 micrograms) had no effect. The degree of attenuation of LC sensory responses by CRF was not linearly related to the magnitude of CRF-induced increases in spontaneous discharge rate, suggesting that these are distinct effects of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of corticotropin-releasing factor on plasma motilin and somatostatin levels and gastrointestinal motility in dogs

The effects of intracerebroventricular and intravenous administration of corticotropin-releasing factor (CRF) on gastrointestinal motility, motilin-induced gastric motor response, and plasma motilin and somatostatin levels were investigated in fasted dogs chronically prepared with strain gauge transducers on the antrum and proximal jejunum. Administered intracerebroventricularly at doses of 20 and 100 ng/kg in fasted dogs, CRF suppressed for 4–5 h the gastric cyclic migrating motor complex. A similar dose (100 ng/kg) administered intravenously was inactive. Corticotropin-releasing factor administration by the intravenous route at 100 ng/kg did not alter the cyclic plasma motilin and somatostatin variations associated with the cyclic gastric motor events. During the blockade of antral migrating motor complex induced by intracerebroventricular administration of CRF, cyclic peaks of plasma motilin were absent whereas those of somatostatin persisted. The gastrointestinal migrating motor complex induced by the intravenous administration of porcine motilin (0.25 μg/kg) was abolished when motilin was injected 2 h after the intravenous administration of CRF (100 ng/kg), whereas a similar dose of CRF administered intracerebroventricularly did not abolish the antral and jejunal motor responses to motilin. It is concluded that in fasted dogs, CRF administered centrally affects the interdigestive gastric motility and the release of motilin but not that of somatostatin. These results also suggest that (a) the intracerebroventricular CRF-induced blockade of motilin release is responsible for the inhibition of gastric migrating motor complex and (b) circulating CRF is able to affect the gastric motor response to porcine motilin through a peripheral mechanism that does not involve somatostatin and motilin secretion.

Corticotropin-releasing factor (CRF) — a review

Corticotropin-releasing factor (CRF), a 41 amino acid polypeptide, has been isolated from ovine hypothalamic extracts, sequenced, and synthesized. It has a high potency for stimulating the secretion of corticotropin-like and β-endorphin-like immunoactive substances in vitro and in vivo in laboratory animals and humans. The high concentration of CRF-like immunoactivity in hypophyseal portal plasma supports the hypothesis that CRF is the physiological hypothalamic factor. Human and rat CRF (rCRF) also have been purified and synthesized. They have an 83% sequence homology with ovine CRF (oCRF). oCRF-like activity has been found in human hypothalamus, pituitary stalk, posterior pituitary, thalamus, cerebral cortex, cerebellum, pons, medulla oblongata, spinal cord and in the adrenal, lung, liver, stomach, duodenum and pancreas. oCRF-like activity also has been found in the human placenta and in tissues producing ectopic ACTH. The action of CRF can be potentiated by vasopressin, oxytocin, epinephrine, norepinephrine, VIP, and angiotensin II. Intracerebroventricular administration of CRF in the rat produces prolonged elevations of plasma epinephrine, norepinephrine, glucose and glucagon; elevates mean arterial pressure and heart rate; increases motor activity and exploration in familiar surroundings and oxygen consumption; and decreases feeding and sexual behavior. Testing with CRF has enabled the separation of patients with hypothalamic and pituitary adrenal insufficiency. The CRF stimulation test has been useful in distinguishing pituitary from ectopic causes of Cushing's disease. The distribution of CRF within and beyond the hypothalamus provides an anatomical context for the observation that CRF can simultaneously activate and coordinate metabolic, circulatory and behavioral responses that are adaptative in ‘stressful’ situations. CRF not only stimulates the pituitary - adrenal axis in man, but it also influences several aspects of CNS function which may be of relevance to psychiatric illnesses.

Corticotropin-releasing factor and angiotensin II: Comparison of CNS actions to influence neuroendocrine and cardiovascular function

The cardiovascular and hormonal responses to intracerebroventricular administration of corticotropin-releasing factor (CRF) and angiotensin II (AII) were compared in conscious, freely moving rats. CRF elevated mean arterial pressure (MAP) and heart rate (HR), increased plasma catecholamine levels and had no effect on plasma vasopressin levels. AII increased MAP and decreased HR, had no effect on plasma catecholamine levels and elevated plasma vasopressin levels. Ganglionic blockade with chlorisondamine blocked the cardiovascular effects of CRF but failed to antagonize the pressor response to AII. The vasopressin antagonist, [1-deaminopenicillamine, 2-(0-methyl)tyrosine]-AVP, did not modify CRF-induced cardiovascular changes but greatly attenuated AII's effects on blood pressure. These results suggest that CRF and AII have different central actions on hormonal and cardiovascular systems.

Corticotropin-releasing factor (CRF): central effects on mean arterial pressure and heart rate in rats.

Intracerebroventricular administration of corticotropin-releasing factor (CRF) produces elevations in mean arterial pressure and heart rate in conscious freely-moving rats. Pretreatment with the ganglionic blocker, chlorisondamine, completely prevents the CRF-induced cardiovascular changes. These results suggest that CRF acts within the brain to stimulate sympathetic nervous activity which in turn influences cardiovascular function.